Hyperparathyroidism

Hyperparathyroidism (HPT) is a medical condition in which the parathyroid glands produce excessive amounts of parathyroid hormone (PTH) in the blood. HPT has many difficult symptoms, including muscle weakness, bone and joint pain, concentration and memory issues, abdominal pain, and frequent urination. Some patients with HPT may also feel a lump in the neck.

HPT is treatable, especially if caught early, but leaving it untreated can lead to life-threatening complications such as osteoporosis and kidney disease. Not only that, but HPT is also linked to several types of cancers. In this article, we’ll explore the connection between hyperparathyroidism and cancer.

What is Hyperparathyroidism?

PTH maintains steady levels of calcium in the blood. HPT occurs when one or more of the parathyroid glands become enlarged and produce large amounts of parathyroid hormone. A high level of PTH leads to high calcium levels in the blood, impacting various body systems including the bones and muscles, brain, gastrointestinal system, and kidneys.

Hyperparathyroidism in Cancer Patients

A growing body of scientific evidence tells us that HPT is associated with numerous cancer types, including parathyroid cancer and thyroid cancer as well as skin, breast, colon, rectal, and kidney cancers. Studies also show that HPT increases the risk of malignant cancers. A study based on data from the Danish cancer care registry showed that patients with HPT have 25% increased risk of cancers.

Hyperparathyroidism and Parathyroid Cancers

Around 0.5% to 5% of HPT is caused by parathyroid cancer—that is, by a malignant tumor in the parathyroid. As of now, we know that certain factors, such as radiation therapy in the head, neck or breast region, and genetic disorders like hyperparathyroidism-jaw tumor syndrome, multiple endocrine neoplasia type I (MEN1) and familial isolated hyperparathyroidism (FIHP), increase the risk of parathyroid cancer.

High calcium levels in blood is one of the chief indicators of HPT, and thus the risk of parathyroid cancer. If your blood reports show high serum calcium levels or if you experience any of the symptoms discussed above, you should get a consult from a board-certified parathyroid specialist.

Parathyroid cancers are aggressive cancers and should be caught and treated early. For this condition, the only treatment is the complete removal of the affected parathyroid gland. If the tumor isn’t removed completely, recurrence of the cancer is extremely likely.

Hyperparathyroidism and Thyroid Cancer

A study published in BMC Surgery showed that the incidence of papillary thyroid cancer is high in patients with primary and secondary HPT. Papillary thyroid cancer is the most common type of thyroid cancer, which usually forms on one lobe of the thyroid gland. The study also found that thyroid tumors more than 1 cm in size were seen only in patients with primary hyperparathyroidism.

Thyroid cancer spreads very fast and can affect the lungs, bones and other body parts. Its symptoms include persistent cough, hoarseness of voice, neck pain which radiates to the ear, swelling in the neck, and difficulty breathing and swallowing. If you experience any of these symptoms alongside the symptoms of HPT described above, it is likely your HPT may have led to thyroid cancer. Consult a thyroid specialist immediately.

Hyperparathyroidism and Breast Cancer

Breast cancer is among the leading cancers in women in the US. Around 30-40% of women with malignant breast cancers do show high calcium levels in blood at some point during their illness. In these cases, high calcium levels in blood usually indicate spread of cancer to the bones, but it may also be caused by primary hyperparathyroidism. Moreover, women with primary hyperparathyroidism are more likely to have breast cancer than women who don’t. In women with breast cancer and high serum calcium levels, parathyroid hormone levels are usually checked to find out if the underlying cause of high calcium levels is HPT.

The Hyperparathyroidism and Cancer Connection—Possible Theories

So, we know that HPT and cancers are associated, but how do we explain the link between them? There are several theories that have been proposed so far.

Some research shows that high calcium levels in blood triggers cell division. Cancer cells, by nature, do not stop multiplying or die off, so runaway cell division caused by high blood calcium levels could conceivably lead to cancerous growth.

A few studies have also pointed out that high parathyroid hormone levels promote tumor development and inhibit cell death. Some other studies say that low levels of vitamin D, which is a prominent feature of HPT, may also increase cancer risk.

The evidence shared by these studies, however, is unfortunately not yet definitive. Scientists are still trying to find out the exact mechanisms that explain why cancer and HPT coexist, so for the moment these theories are not yet proven.

When to See a Doctor about HPT

As noted above, untreated HPT may lead to serious health issues. Many studies have shown that in addition to cancer, HPT is also linked with life threatening heart and kidney disease. Hence, it is important to be watchful for hyperparathyroidism symptoms and signs, and if you have HPT, get it treated early to prevent complications.

If you experience symptoms of HPT and your blood reports show alterations in P and calcium levels, you should get an appointment with a parathyroid expert. Dr. Babak Larian of the CENTER for Advanced Parathyroid Surgery is a parathyroid expert in treating HPT safely and effectively. He performs a minimally invasive parathyroidectomy (MIP) with a high success rate and minimal scarring. An MIP can usually be completed in under 20 minutes and is followed by a four-gland assessment that ensures patients can maximize their surgery results.

References:

1. HyperparathyroidMD. Is there a connection between hyperparathyroidism and cancer. Available at:

2. Pickard AL, Gridley G, Mellemkjae L, Johansen C, Kofoed-Enevoldsen A, Cantor KP, Brinton LA. Hyperparathyroidism and subsequent cancer risk in Denmark. Cancer. 2002 Oct 15;95(8):1611-7. doi: 10.0.3.234/cncr.10846. PMID: 12365007.

3. Serena Palmieri, Letizia Roggero, Elisa Cairoli, Valentina Morelli, Alfredo Scillitani, Iacopo Chiodini, Cristina Eller-Vainicher . Occurrence of malignant neoplasia in patients with primary hyperparathyroidism. European Journal of Internal Medicine. Volume 43, September 2017, Pages 77-82

4. Michels KB, Xue F, Brandt L, Ekbom A. Hyperparathyroidism and subsequent incidence of breast cancer. Int J Cancer. 2004 Jun 20;110(3):449-51. doi: 10.0.3.234/ijc.20155. PMID: 15095313.

5. Rodrigo Arrangoiz, et al. Is Breast Cancer Associated with Primary Hyperparathyroidism?. American Journal of Otolaryngology and Head and Neck Surgery.2019. Volume 2(1). Article 1033

6. Goswami S, Ghosh S. Hyperparathyroidism: cancer and mortality. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S217-20. doi: 10.0.16.7/2230-8210.104042. PMID: 23565381; PMCID: PMC3603029.

7. Karaköse M, Kocabaş M, Can M, Çalışkan Burgucu H, Çordan İ, Kulaksızoğlu M, Karakurt F. Increased incidence of malignancy in patients with primary hyperparathyroidism. Turk J Med Sci. 2021 Aug 30;51(4):2023-2028. doi: 10.0.15.66/sag-2012-18. PMID: 33957725; PMCID: PMC8569777.

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Part 1 of 3 A Common Guide to Hyperparathyroidism:

Most people know that they have a thyroid gland, but the parathyroid glands that sit just behind the thyroid get less attention. The four parathyroid glands are about the size of a grain of rice, and they perform an essential function: releasing parathyroid hormone (PTH), which regulates calcium, magnesium, and phosphorus levels in the body.

For a snapshot of what this looks like, let’s take a look at calcium. This mineral plays a crucial role in bone strength, proper muscle contraction, nerve function, and blood clotting. Roughly 99% of the body’s calcium is stored in the bones. The other 1% is in the blood and tissues. The parathyroid hormone helps balance the amount of calcium in the blood. If the blood calcium level drops, PTH will prompt the bones to release calcium into the bloodstream.

When more calcium is needed in the bloodstream, PTH helps release the mineral from our bones so it can enter the bloodstream and travel to the tissues that need it. Additionally, PTH can use vitamin D to help the intestines absorb calcium from food and helps prevent the kidneys from flushing too much calcium in the urine.

What is Hyperparathyroidism and Who Does it Affect?

Hyperparathyroidism is when the parathyroid glands stop working as they should, producing an excess of parathyroid hormone (PTH). This overabundance of PTH plays a role in pulling too much calcium from the bones, which can cause bone fragility and osteoporosis. Excessive calcium in the bloodstream can also cause kidney stones, joint and muscle pain, fatigue, abdominal upset, depression, and a general feeling of discomfort.

For reference, a normal parathyroid hormone level is 14 to 65 picograms (pg) per milliliter (mL). A normal blood calcium level is 8.6 to 10.3 milligrams (mg) per deciliter (dL).

Hyperparathyroidism tends to affect people over the age of 60 and women in particular. Other risk factors for the condition include people who have had radiation therapy in the neck area, people with ongoing, acute Vitamin D or calcium deficiencies, and patients who take lithium. There are three main types of hyperparathyroidism: primary, secondary, and tertiary.

The Difference Between Primary, Secondary, and Tertiary Hyperparathyroidism:

Several factors can influence how much parathyroid hormone the parathyroid glands produce. Each type of hyperparathyroidism can have different symptoms and causes. Knowing the difference between the three can help patients decide which type of care to seek out. It’s important to seek out medical care if you are experiencing any of the symptoms of HPT. Left untreated, HPT only gets worse, causing bone, kidney, and even heart problems.

Primary Hyperparathyroidism:

With primary hyperparathyroidism, the cause is an enlarged parathyroid gland that produces too much PTH, causing blood calcium levels to rise. Parathyroid gland enlargement can be caused by:

Adenoma: An adenoma is a benign tumor, which is usually present only in one gland. This type of enlargement causes approximately 85% of hyperparathyroidism cases.

Hyperplasia: The presence of abnormal cells in each gland is called hyperplasia. Hyperplasia causes all four glands to enlarge and malfunction, and roughly 15% of hyperparathyroidism cases are caused by this condition.

Parathyroid Cancer: Most hyperparathyroidism patients do not have parathyroid cancer, as cancerous cells cause less than 1% of all HPT cases, but it is a potential cause of hyperparathyroidism.

The most common symptoms of primary hyperparathyroidism are frequent urination, constipation, excessive thirst, joint pain, abdominal pain, lethargy, weakness, bone pain and/or fragility fractures, nausea, vomiting, and memory loss.

Because primary hyperparathyroidism is caused by abnormal cells or growth in one or more parathyroid glands, the most effective treatment is surgery to remove the dysfunctional gland. While the idea of neck surgery can be intimidating, a skilled parathyroid surgeon can perform a minimally invasive parathyroidectomy with intraoperative parathyroid testing to ensure a high level of success. With a minimally invasive parathyroidectomy, surgeons utilize local anesthesia instead of general anesthesia, meaning patients do not need to have a breathing tube or stay in a hospital overnight. The incision on a minimally invasive parathyroidectomy is smaller and can be blended into the neck’s natural creases, and recovery time tends to be shorter than it is with a more involved surgery.

Secondary Hyperparathyroidism:

Secondary hyperparathyroidism happens when a condition outside of the parathyroid glands causes all four glands to enlarge and release an excess of PTH. The most common causes of

Part 2 of 3 secondary hyperparathyroidism are severe vitamin D deficiency and kidney failure.

When kidney failure occurs, the kidneys cannot make vitamin D or flush the phosphorus in the body. This is problematic because vitamin D helps the body absorb calcium, and excessive phosphorus can limit calcium absorption. With kidney failure or low vitamin D, a person is at risk of blood calcium deficiency. The low blood calcium level stimulates PTH production in the parathyroid hormones. This constant stimulation, in turn, can lead to overactive, enlarged parathyroid glands.

Patients with kidney failure and secondary hyperparathyroidism may have PTH levels in the hundreds or thousands, which is far beyond the normal upper limit of 65 pg/mL. Without treatment, these extreme PTH levels can cause calcium deposits to form in the muscles and skin (calciphylaxis). This is a serious, life-threatening condition that can lead to ulcers, gangrene, and even death.

Symptoms of secondary hyperparathyroidism are similar to those that occur with primary HPT: abdominal pain, osteoporosis, nausea, vomiting, kidney stones, appetite loss, and weakness.

With secondary hyperparathyroidism, the first line of treatment should be to take care of kidney failure or vitamin D deficiency. Kidney failure is often treated with a kidney transplant or with dialysis. Once the primary cause of secondary hyperparathyroidism has been addressed, medications to help regulate PTH and calcium levels can help restore a more normal parathyroid function. In some cases, however, surgery may be needed.

Tertiary Hyperparathyroidism:

If secondary HPT is left untreated, or if it persists even after a kidney transplant or dialysis, it becomes tertiary hyperparathyroidism. Because tertiary HPT is essentially advanced secondary HPT, the symptoms can be more severe and may include:

Uncontrollably itchy skin (pruritis)

Bone pain and fractures

Vascular or soft tissue calcifications

Inflammation in the pancreas (pancreatitis)

Kidney stones

Calciphylaxis, a life-threatening condition

Parathyroid surgery is required to treat tertiary hyperparathyroidism.

Next Steps After Being Diagnosed with Hyperparathyroidism:

Once you seek out medical care for your HPT symptoms, your doctor can order blood tests and perform scans to confirm a diagnosis. Then, you and your doctor can discuss the best treatment options.

Being diagnosed with hyperparathyroidism can be overwhelming. The good news is that a highly skilled parathyroid surgeon can help cure primary hyperparathyroidism and treat secondary and tertiary hyperparathyroidism once the underlying issue has been addressed.

Primary hyperparathyroidism caused by a parathyroid adenoma is the most common form of HPT. Minimally invasive parathyroidectomy can treat this type of HPT in most cases because the surgery has a high cure rate.

This is especially true if the parathyroidectomy is performed by a surgeon who does rapid intraoperative PTH testing, in which the surgeon tests the patient’s parathyroid hormone before the surgery to get a baseline level and then again after the parathyroid has been removed—but before the surgery is completed. Rapid intraoperative PTH testing helps the surgeon make sure that the remaining parathyroid glands are functioning normally. If they aren’t, additional steps can be taken to treat the issue while the patient is still in surgery, thus minimizing the need for additional surgeries and ensuring a higher cure rate.

At the CENTER for Advanced Parathyroid Surgery, Babak Larian, MD, FACS, uses intraoperative PTH testing and has a parathyroidectomy cure rate above 97%. He also treats primary hyperparathyroidism caused by parathyroid hyperplasia and parathyroid cancer. Dr. Larian can also perform surgery if needed for secondary or tertiary hyperparathyroidism.

Parathyroid surgery can cure your hyperparathyroidism and bring you relief from the debilitating symptoms that come with it, often within just two to four days after surgery. You’ll be able to go home the same day and return to your normal activities within one to three weeks.

To learn more about how to lessen your HPT symptoms, contact Dr. Babak Larian of the CENTER for Advanced Parathyroid Surgery. His goal is to make every patient he treats feel welcomed, listened to, and fully informed before, during, and after parathyroid treatment.

Sources:

www.hyperparathyroidmd.com

https://www.uclahealth.org/endocrine-center/parathyroid-hyperplasia

https://www.uclahealth.org/medical-services/surgery/endocrine-surgery/patient-resources/patient-education/normal-calcium-levels

https://www.hopkinsmedicine.org/health/cond

Part 3 of 3 itions-and-diseases/hyperparathyroidism

https://www.hopkinsmedicine.org/health/conditions-and-diseases/primary-hyperparathyroidism

https://columbiasurgery.org/conditions-and-treatments/secondary-hyperparathyroidism

https://www.kidney.org/atoz/content/choosingtreat

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